Cell shape is a fundamental biological feature, providing specific information about physiological or pathological cellular conditions. Most of the state-of-the-art microfluidic cytometers, however, only allow simple cell analysis, including viability studies, cell counting and sorting. In this work, we present a non-invasive, label-free device capable of single cell morphology discrimination in continuous flow. The device is based on the principle of liquid electrodes, fabricated in a cross configuration around a sensing zone. This arrangement allows measurement of cell impedance along orthogonal orientations and extraction of an index describing cell shape anisotropy. By adding prior to the sensing volume a series of lateral liquid electrodes, the particle stream was focused toward the channel midline and each cell was oriented in a specific direction before shape sensing. We demonstrate the proof of concept by performing spherical and elongated particle discrimination. As an application, we show that the shape changes experienced during cell division can be monitored and characterized. In particular, budding yeasts at different stages of the mitotic cycle were identified by extracting their anisotropy index.
The performance of a novel microfluidic impedance cytometer [1] for single-cell analysis is investigated in-silico by means of a finite element model. The main feature of the device is the ability to probe impedance of flowing cells along two orthogonal directions. As proved by means of numerical simulations involving spherical and ellipsoidal cells, this allows to extract information on cell morphology. In particular, simple anisotropy indices are devised, which are independent from cell volume and rather insensitive to small imperfections in the focusing system. In addition, simulations with budding yeasts show the capability of the device to identify the cell division stage
In today’s highly integrated microelectronic systems there is a need for high-resolution spatial temperature measurement on chips. The resolution requirements are higher than the infrared imaging systems are capable of, and the investigated areas of the chips are often too large for most common scanning thermal microscopes. In this article we present two quantitative methods to acquire a thermal map with high resolution over a large area. We use two approaches: a noncontact method based on infrared radiation and scanning thermal microscopy (SThM). In both methods the expected thermal properties of the sample were thoroughly calculated and the prediction was in agreement with the experimental results. For the study of infrared radiation the composition of the sample together with the spectral sensitivity of the sensor were taken into account. In the SThM part, there were discrepancies based on unequal conditions during calibration and subsequent measurement. Using a finite element method simulation of the thermal field, the problem has been solved and successfully experimentally verified. For both methods a special sample with an embedded thermometer capable of being heated internally or externally was used.
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